Genmab A/S (NASDAQ: GMAB) has reported compelling results from its pivotal Phase 3 EPCORE® FL-1 trial, demonstrating that the combination of EPKINLY® (epcoritamab-bysp) with rituximab and lenalidomide reduced the risk of disease progression or death by 79 percent compared to the standard R2 regimen in relapsed or refractory follicular lymphoma (FL). The trial’s data, which was simultaneously published in The Lancet and presented at the 67th American Society of Hematology (ASH) Annual Meeting, has catalyzed regulatory progress, culminating in U.S. Food and Drug Administration approval of the EPKINLY + R2 regimen for second-line use in November 2025.
The results are being interpreted by analysts as a potential inflection point for bispecific antibody therapies in hematologic malignancies. Epcoritamab, which binds to CD3 on T cells and CD20 on B cells to direct T-cell-mediated killing of malignant B cells, is part of Genmab’s growing portfolio of DuoBody®-based biologics. It is co-developed and co-commercialized with AbbVie Inc., who is leading global commercialization outside the United States and Japan.
How does EPKINLY plus R2 stack up against standard second-line follicular lymphoma treatment?
The EPCORE FL-1 study enrolled adult patients with relapsed or refractory FL who had received at least one prior systemic therapy. Patients were randomized to receive either EPKINLY in combination with rituximab and lenalidomide (n=243) or rituximab and lenalidomide alone (n=245). Treatment in the experimental arm followed 28-day cycles, administered for up to 12 cycles or until progression or toxicity.
In terms of efficacy, the combination delivered a 95 percent overall response rate, with 83 percent of patients achieving a complete response. In contrast, the R2-only group saw a 79 percent overall response rate and a 50 percent complete response rate. These results were highly statistically significant, with a p-value of less than 0.0001.
The median follow-up period was 14.8 months at the time of the second interim analysis. Duration of response at 12 months was observed in 89 percent of patients receiving EPKINLY + R2, compared to 49 percent in the R2 arm. The hazard ratio for progression-free survival was 0.21, meaning patients treated with the bispecific combination experienced nearly an 80 percent reduction in risk of progression or death.
What safety issues were flagged in the EPCORE FL-1 trial, and how manageable are they?
While the efficacy results were striking, safety outcomes indicated an elevated toxicity profile in the EPKINLY + R2 group, particularly in terms of neutropenia and infection risk. Grade 3 or 4 treatment-emergent adverse events occurred in 90.1 percent of patients on EPKINLY + R2, compared to 67.6 percent of those on R2 alone. Neutropenia was observed in 68.7 percent of patients on the combination regimen, while only 42 percent of the control group experienced it. Similarly, infections were significantly more frequent and severe in the combination arm.
Despite the higher frequency of Grade 3 or 4 adverse events, fatal treatment-related events occurred less often in the EPKINLY + R2 group at 1.6 percent, versus 3.8 percent in the R2 group. Cytokine release syndrome, a concern with bispecifics, was reported in 26.3 percent of patients but was limited to Grade 1 or 2 in severity, owing to the use of a three-step dosing protocol.
Discontinuation due to adverse events was also higher in the combination arm, occurring in 18.9 percent of patients, compared to 12.2 percent in the control arm. Nonetheless, oncologists at ASH 2025 suggested that the improved efficacy may justify the elevated toxicity profile for many eligible patients.
What is Epcoritamab and how is it designed to work in B-cell malignancies?
Epcoritamab is a subcutaneously administered bispecific antibody developed using Genmab’s DuoBody-CD3 platform, which aims to harness the cytotoxic potential of T cells. By simultaneously targeting CD3 on T cells and CD20 on B cells, Epcoritamab redirects T cells to recognize and eliminate malignant B cells expressing CD20.
Unlike traditional monoclonal antibodies or checkpoint inhibitors, bispecifics like Epcoritamab offer a direct mechanism for immune cell engagement. This can be particularly useful in relapsed or refractory disease settings where the immune system has become desensitized or immune escape mechanisms are present.
Epcoritamab is marketed under the name EPKINLY in the United States and Japan and TEPKINLY in the European Union. It is already approved for relapsed/refractory FL after two or more prior treatments, and the latest U.S. approval expands its indication to patients who have failed just one line of systemic therapy.
How does Genmab and AbbVie’s broader trial strategy support Epcoritamab’s growth?
Beyond FL, Genmab and AbbVie are running several Phase 3 trials to further expand Epcoritamab’s clinical footprint. These include monotherapy and combination studies across multiple forms of non-Hodgkin lymphoma. Current trials include:
A study comparing Epcoritamab monotherapy to investigator’s choice chemotherapy in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) (NCT04628494).
A first-line DLBCL study evaluating Epcoritamab with R-CHOP chemotherapy (NCT05578976).
A Phase 3 trial assessing Epcoritamab plus R2 versus chemoimmunotherapy in previously untreated FL (NCT06191744).
A DLBCL trial evaluating Epcoritamab with lenalidomide compared to standard chemotherapy infusions (NCT06508658).
These trials are structured to test Epcoritamab across the full disease continuum, from first-line to relapsed or refractory settings. The companies are also pursuing additional regulatory approvals globally, with AbbVie leading efforts outside North America.
What is the broader market and clinical context for follicular lymphoma treatment?
Follicular lymphoma is an indolent but incurable subtype of non-Hodgkin lymphoma, accounting for 20 to 30 percent of NHL cases. In the United States, approximately 15,000 new diagnoses are made annually. Current standard therapies often fail to deliver lasting remissions, and patients experience progressively shorter responses with each relapse.
Over time, nearly one in four FL patients experience histologic transformation to aggressive DLBCL, which carries significantly worse survival rates. While chemoimmunotherapy has long been the standard of care, there has been growing demand for chemotherapy-free regimens that deliver durable efficacy with improved quality of life.
The emergence of bispecific antibodies, including Epcoritamab, represents a novel class of immunotherapies that seek to meet this clinical need. By eliminating the need for chemotherapy in certain treatment settings, Epcoritamab offers the potential for disease control with fewer long-term toxicities.
How is investor sentiment shaping around Genmab’s commercial strategy?
Genmab shares (NASDAQ: GMAB) have remained stable post-approval, reflecting both investor optimism and cautious macro sentiment in biotech. Analysts following the company believe the EPCORE FL-1 data validates the broader DuoBody platform, positioning Genmab as a leader in bispecific development alongside companies such as Regeneron and Roche.
While AbbVie’s co-commercialization role will impact profit-sharing, it also significantly de-risks international market access. Commercial execution and future label expansions are expected to be key drivers for revenue growth starting in fiscal 2026.
Market analysts expect Epcoritamab to generate over $1 billion in peak sales if it secures additional indications in DLBCL and first-line FL. However, reimbursement dynamics, real-world adverse event rates, and competitive launches from other bispecifics or CAR-T therapies could influence the uptake trajectory.
What are the key takeaways from Genmab’s EPCORE FL-1 trial and FDA approval?
- Genmab’s Epcoritamab + R2 combination demonstrated a 79 percent reduction in risk of disease progression or death in relapsed/refractory follicular lymphoma.
- The regimen achieved a 95 percent overall response rate and an 83 percent complete response rate, outperforming standard R2 therapy across endpoints.
- The U.S. FDA approved the combination in November 2025 for use after one or more prior systemic therapies.
- Safety profile included higher Grade 3/4 adverse events, primarily neutropenia and infections, though fatal events were lower than in the control arm.
- Cytokine release syndrome was manageable under a step-up dosing protocol, with no Grade 3/4 events reported.
- Epcoritamab is being evaluated in additional Phase 3 studies across DLBCL and FL indications, including frontline use.
- Analysts view Epcoritamab as a high-potential bispecific therapy that could disrupt current lymphoma treatment paradigms.
- Genmab and AbbVie aim to expand commercial access through global partnerships and label expansion efforts.
Discover more from Business-News-Today.com
Subscribe to get the latest posts sent to your email.
